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Small-Molecule Inhibitors and Degraders Targeting KRAS-Driven Cancers

Drug resistance continues to be a major problem associated with cancer treatment. One of the primary causes of anticancer drug resistance is the frequently mutated RAS gene. In particular, considerable efforts have been made to treat KRAS-induced cancers by directly and indirectly controlling the ac...

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Detalles Bibliográficos
Autores principales: Hyun, Soonsil, Shin, Dongyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621880/
https://www.ncbi.nlm.nih.gov/pubmed/34830024
http://dx.doi.org/10.3390/ijms222212142
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author Hyun, Soonsil
Shin, Dongyun
author_facet Hyun, Soonsil
Shin, Dongyun
author_sort Hyun, Soonsil
collection PubMed
description Drug resistance continues to be a major problem associated with cancer treatment. One of the primary causes of anticancer drug resistance is the frequently mutated RAS gene. In particular, considerable efforts have been made to treat KRAS-induced cancers by directly and indirectly controlling the activity of KRAS. However, the RAS protein is still one of the most prominent targets for drugs in cancer treatment. Recently, novel targeted protein degradation (TPD) strategies, such as proteolysis-targeting chimeras, have been developed to render “undruggable” targets druggable and overcome drug resistance and mutation problems. In this study, we discuss small-molecule inhibitors, TPD-based small-molecule chemicals for targeting RAS pathway proteins, and their potential applications for treating KRAS-mutant cancers. Novel TPD strategies are expected to serve as promising therapeutic methods for treating tumor patients with KRAS mutations.
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spelling pubmed-86218802021-11-27 Small-Molecule Inhibitors and Degraders Targeting KRAS-Driven Cancers Hyun, Soonsil Shin, Dongyun Int J Mol Sci Review Drug resistance continues to be a major problem associated with cancer treatment. One of the primary causes of anticancer drug resistance is the frequently mutated RAS gene. In particular, considerable efforts have been made to treat KRAS-induced cancers by directly and indirectly controlling the activity of KRAS. However, the RAS protein is still one of the most prominent targets for drugs in cancer treatment. Recently, novel targeted protein degradation (TPD) strategies, such as proteolysis-targeting chimeras, have been developed to render “undruggable” targets druggable and overcome drug resistance and mutation problems. In this study, we discuss small-molecule inhibitors, TPD-based small-molecule chemicals for targeting RAS pathway proteins, and their potential applications for treating KRAS-mutant cancers. Novel TPD strategies are expected to serve as promising therapeutic methods for treating tumor patients with KRAS mutations. MDPI 2021-11-09 /pmc/articles/PMC8621880/ /pubmed/34830024 http://dx.doi.org/10.3390/ijms222212142 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hyun, Soonsil
Shin, Dongyun
Small-Molecule Inhibitors and Degraders Targeting KRAS-Driven Cancers
title Small-Molecule Inhibitors and Degraders Targeting KRAS-Driven Cancers
title_full Small-Molecule Inhibitors and Degraders Targeting KRAS-Driven Cancers
title_fullStr Small-Molecule Inhibitors and Degraders Targeting KRAS-Driven Cancers
title_full_unstemmed Small-Molecule Inhibitors and Degraders Targeting KRAS-Driven Cancers
title_short Small-Molecule Inhibitors and Degraders Targeting KRAS-Driven Cancers
title_sort small-molecule inhibitors and degraders targeting kras-driven cancers
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621880/
https://www.ncbi.nlm.nih.gov/pubmed/34830024
http://dx.doi.org/10.3390/ijms222212142
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